EXCEED THE SPACE PROVIDED. This is a resubmission of a competitive renewal application for the General Clinical Research Center (GCRC) at Beth Israel Deaconess Medical Center (BIDMC) and our two satellites at the Joslin Diabetes Center and the Forsyth Institute. We ask for continued support to extend our successful 30-year history. The proposal provides an overview of the rich and diverse research conducted by investigators at our GCRC, documenting the active collaborations and sharing of resources among various disciplines and departments. Translational research efforts, converting insights from the laboratory into the safest, best- designed and controlled clinical trials to address human diseases that have major health care impact, continue to be the primary goal of our GCRC. In addition, we remain committed to the education of young investigators and future leaders in clinical research through a growing number of teaching and training programs in which the GCRC plays a crucial role. We have carefully considered the input from the reviewers of our initial submission and have followed their various suggestions as detailed in our Introduction (page 485). We have changed some of the main presentations to provide a better overview of the outstanding science being conducted at our GCRC, and our Institutional Review Board has implemented a number of changes to the review and approval process of new studies. This will allow us to continue to assure the safest possible environment for our research subjects. Specific areas of investigation that are highlighted in this application include: 1) pathophysiology of obstructive sleep apnea, 2) plasticity of the brain following loss of vision, 3) decitabine alteration of gene expression profile of tumor cells, potentially increasing their sensitivity to dacarbazine, 4) role of blood pressure on vasoregulation and cerebral perfusion in elderly patients after stroke, 5) potential use of leptin in the treatment of amenorrhea, infertility, and bone loss in women with hypothalamic dysfunction, 6) role of the oral microbiota in refractory and treatable periodontitis, and 7) the role of insulin in regulating ft-cell function in healthy and insulin resistant populations.